The growth of recombinant DNA technology in recent years has led to the introduction of vaccines in which an immunogenic protein has been identified, cloned and expressed in a suitable host to obtain sufficient quantities of protein to allow effective protective immunization in both animals and humans. Many of the most effective vaccines are based on the potent ability of virion surfaces to elicit neutralizing antibodies. These include licensed killed or attenuated virus vaccines, such as polio, influenza and rabies, which effectively induce protective antibody responses. More recently, subunit vaccines based upon self-assemblages of the structural proteins of human papillomavirus (HPV) and hepatitis B virus (HBV) have been approved by the Food and Drug Administration.
Phage display is one of several technologies that make possible the presentation of large libraries of random amino acid sequences with the purpose of selecting from them peptides with certain specific functions. The basic idea is to create recombinant bacteriophage genomes containing a library of randomized sequences genetically fused to one of the structural proteins of the virion. When such recombinants are transfected into bacteria each produces virus particles that display a particular peptide on their surface and which package the same recombinant genome that encodes that peptide, thus establishing the linkage of genotype and phenotype essential to the method. Arbitrary functions (e.g. the binding of a receptor, immunogenicity) can be selected from such libraries by the use of biopanning and other techniques. Because of constraints imposed by the need to transform and subsequently cultivate bacteria, the practical upper limit on peptide library complexity in phage display is said to be around 1010-1011 [Smothers et al., 2002, Science 298:621-622]. This requirement for passage through E. coli is the result of the relatively complex makeup of the virions of the phages used for phage display, and the consequent necessity that their components be synthesized and assembled in vivo. For example, display of certain peptides is restricted when filamentous phage is used, or not possible, since the fused peptide has to be secreted through the E. coli membranes as part of the phage assembly apparatus.